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Molecular Biology Reports

, Volume 47, Issue 2, pp 1173–1185 | Cite as

Lawsone, a 2-hydroxy-1,4-naphthoquinone from Lawsonia inermis (henna), produces mitochondrial dysfunctions and triggers mitophagy in Saccharomyces cerevisiae

  • Mariana Rodrigues Xavier
  • Manuella Maria Silva Santos
  • Maise Gomes Queiroz
  • Mariza S. de Lima Silva
  • Alexandre José S. Goes
  • Marcos Antonio De Morais JrEmail author
Original Article
  • 63 Downloads

Abstract

Lawsone is a natural naphthoquinone present in the henna leaf extract with several cytotoxic activities and used as precursor for synthesis of various pharmaceutical compounds. Its biological activities are thought to be the result of oxidative stress generated, although the hydroxy group at position C-2 in its structure tends to reduce its electrophilic potential. In view of lack of knowledge on its activity, the present work aimed to elucidate the biological effect of lawsone using the yeast Saccharomyces cerevisiae. In the model strain BY4741 it was defined 229 mmol/L as the minimal inhibitory concentration (MIC). Using 172 mmol/L as sub-MIC value it was observed that yap1 deletion mutant was sensitive to lawsone independent the presence of oxygen. Lawsone affected yeast growth in glycerol, indicating interference in the respiratory metabolism. Intracellular content of thiol groups did not indicate intensive oxidative stress and the presence of the anti-oxidant N-acetylcysteine (NAC) exacerbated lawsone toxicity. By analysing the sensitivity of atg mutant strains and the localization of GFP-Atg8 fusion protein, it was concluded that lawsone primarily produces mitochondrial malfunctioning, leading to indirect oxidative stress. It triggers the autophagic response that ultimately induces mitophagy.

Keywords

ATG genes Henna Mitochondrial dysfunction Oxidative stress Thiols 

Notes

Acknowledgements

The authors are grateful to Prof. Daniel Klionsky, University of Michigan (USA), for kindly providing atg mutants and GFP-Atg8 fusion construction and to Prof. Andrea Harand, Federal University of Pernambuco (UFPE, Brazil) for the use of fluorescence microscopy. Chemical analyses were performed at the Analytical Centre of the Department of Fundamental Chemistry (UFPE, Brazil). This work was supported with grants from the Brazilian funding agencies FACEPE (project APQ-1452-2.01/10) and CNPq (project 472533/2013-4) and by the research support program of the Federal University of Pernambuco (project 23076.021846/2012-47). MRX and MGQ received master and PhD scholarship supports from CAPES agency and MMOL/LSS received PhD scholarship support from FACEPE agency.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Supplementary material

11033_2019_5218_MOESM1_ESM.docx (435 kb)
Electronic supplementary material 1 (DOCX 435 kb)

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Mariana Rodrigues Xavier
    • 1
  • Manuella Maria Silva Santos
    • 1
  • Maise Gomes Queiroz
    • 1
  • Mariza S. de Lima Silva
    • 2
  • Alexandre José S. Goes
    • 2
  • Marcos Antonio De Morais Jr
    • 1
    Email author
  1. 1.Department of GeneticsFederal University of PernambucoRecifeBrazil
  2. 2.Department of AntibioticsFederal University of PernambucoRecifeBrazil

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